Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors

Yeon Sun Lee, Robert Kupp, Michael V. Remesic, Cyf Ramos-Colon, Sara M Hall, Christopher Chan, David Rankin, Josephine Lai, Frank Porreca, Victor J Hruby

Research output: Contribution to journalLetter

2 Citations (Scopus)

Abstract

As a unique endogenous opioid ligand, dynorphin A shows paradoxical neuroexcitatory effects at bradykinin receptors, and the effects are known to be amplified by the upregulation of dynorphin A under chronic pain and inflammatory conditions. In our earlier structure–activity relationship studies, the amphipathic dynorphin A fragment, [Des-Arg7]-Dyn A-(4–11), was identified as a pharmacophore for the bradykinin receptors along with key structural features. Here, further modifications of the pharmacophore showed that the position of a Pro residue is also an important feature because of its role in making (or disrupting) a β-turn or 310 helix structure which is crucial for receptor recognition.

Original languageEnglish (US)
Pages (from-to)615-619
Number of pages5
JournalChemical Biology and Drug Design
DOIs
StatePublished - Oct 1 2016

Fingerprint

Bradykinin Receptors
Dynorphins
Rats
Brain
Chronic Pain
Opioid Analgesics
Up-Regulation
Ligands

Keywords

  • amphipathicity
  • bradykinin receptors
  • chronic pain
  • non-opioid dynorphin A
  • proline
  • structure–activity relationship

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors. / Lee, Yeon Sun; Kupp, Robert; Remesic, Michael V.; Ramos-Colon, Cyf; Hall, Sara M; Chan, Christopher; Rankin, David; Lai, Josephine; Porreca, Frank; Hruby, Victor J.

In: Chemical Biology and Drug Design, 01.10.2016, p. 615-619.

Research output: Contribution to journalLetter

Lee, Yeon Sun ; Kupp, Robert ; Remesic, Michael V. ; Ramos-Colon, Cyf ; Hall, Sara M ; Chan, Christopher ; Rankin, David ; Lai, Josephine ; Porreca, Frank ; Hruby, Victor J. / Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors. In: Chemical Biology and Drug Design. 2016 ; pp. 615-619.
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AU - Hall, Sara M

AU - Chan, Christopher

AU - Rankin, David

AU - Lai, Josephine

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